The use of caffeine to enhance athletic performance is widely recognized, with numerous studies and meta-analyses proving its benefits for strength, endurance, power and even cognitive function. Despite the vast amount of evidence supporting the effectiveness of caffeine, the number of research into its ergogenic effects continues to grow significantly.
Despite the consolidation of knowledge about caffeine, important gaps in understanding still persist. For this reason, a recent study seeks to identify and justify the main areas that require further investigation, with the aim of guiding future scientific work. The intention is that this research allows the practical application of the ergogenic potential of caffeine in real sporting scenarios, focusing on ten study priorities.
There are still doubts about the ideal dose of caffeine for athletes
The common perception that there is no clear dose-response relationship between caffeine and performance improvement is generally based on meta-analyses that indicated no influence of dosage on the level of benefit. However, this conclusion may be inaccurate due to the complexity of the factors that interact in the response to caffeine, such as the method of administration, circadian variations, exercise modality, the individual’s training level, habitual consumption and even genetics.
Despite the importance of exploring these moderators, the dose-response relationship of acute caffeine ingestion and performance benefit can only be accurately determined through studies that directly compare the effects of different doses under controlled experimental conditions. Surprisingly, specific research on this point is limited.
Few studies have directly investigated this issue. Many demonstrated no benefit at any of the doses tested, while others show effects at a single dose that have not been replicated in different contexts or indicate a similar benefit at multiple dosages. Comparison between previous studies is made difficult by differences in the doses analyzed, the populations studied and the exercise modalities used. Therefore, the current understanding of the caffeine dose-response relationship is still fragile.
Furthermore, the evidence indicates that the link between dose and response may be more intricate than just the magnitude of benefit. For example, research has shown that specific doses of caffeine can increase strength, but only higher doses improve performance in sustained contractions or with higher loads.
The image shows the percentage of participants who reported side effects in relation to increasing the dose of caffeine after a battery of neuromuscular tests. Data were adapted from a study by Pallarés et al., based on 13 resistance-trained men, comparing placebo (PLAC) and caffeine (CAFF) with gastrointestinal (GI) effects included.
It is clear that understanding the caffeine dose-response relationship deserves further investigation. In cases where the caffeine response is binary, future studies are crucial to determine the doses necessary to obtain benefits in various facets of performance and exercise modalities. The lack of direct evidence should not rule out the possibility of a dose-response relationship, as some meta-analyses already suggest that the magnitude of benefit may increase with higher doses.
The debate over the ideal dose of caffeine has expanded with analysis of the effectiveness of lower doses. For many years, 3 mg.kg⁻¹ was considered the minimum dose to improve physical performance. However, there is growing evidence that amounts lower than 3 mg.kg⁻¹, up to 1 mg.kg⁻¹, may be effective in certain aspects of performance, such as vertical jumping.
Studies show that lower doses can provoke a binary response. While 2 mg.kg⁻¹ increased lower body strength in one study, 4 and 6 mg.kg⁻¹ were needed for a small increase in upper body strength. Other work demonstrated that 3 mg.kg⁻¹ improved maximum power, something not observed with 1 mg.kg⁻¹. Although doses below 3 mg.kg⁻¹ may offer specific benefits, most evidence points to a broader range of improvements with doses of 3 mg.kg⁻¹.
The scarcity of studies and the inconsistency of results in this area highlight the need for future research on the effects of low doses of caffeine in different modalities. This type of research is valuable, as doses lower than 3 mg.kg⁻¹ are closer to consumption in commercial products. Benefits at lower doses would be helpful in managing caffeine habituation, as well as being associated with fewer side effects and sleep disturbances. Furthermore, future research could consider the effect of caffeine dose on multiple aspects of performance, as the impact can vary significantly between different physical and cognitive functions.
The temporal evolution of the effects of caffeine on the body
The effects of caffeine on sports performance generally manifest after an optimal intake period, typically about 1 hour before exercise. Although there is evidence of benefits for strength, power, and endurance activities in this range, the full time course of caffeine’s ergogenic effects is not well understood.
Further understanding the duration of caffeine’s effects would be crucial for athletes in long-duration sports or events that span the day. Furthermore, the repeated administration of caffeine, common in sports such as football, has little explored its need and value. While repeated dosing may prolong benefits, it is essential to balance these gains with potential side effects and impact on sleep, considering that caffeine has a half-life of between 1.5 and 9.5 hours.
The duration of ergogenic effects can also be influenced by habitual consumption of the substance. Research has indicated that in individuals who do not consume caffeine regularly, benefits can be seen for up to 6 hours. In regular consumers, performance improved only when ingestion occurred 1 to 3 hours before exercise, suggesting that habituation can alter the time of action of the effects.
One study compared different dosing strategies, including a single high dose, a moderate dose, and repeated doses, in fighters. The results showed that a single high dose improved performance in the first fight, repeated doses benefited intermediate fights, and only an individualized strategy maintained performance until the fifth fight. This suggests that the effects of a single dose may be short-lived, but the effectiveness of repeated dosing is still controversial, with some studies finding no superior benefits.
The route of administration may also influence the duration of the acute effects of caffeine. Caffeine chewing gum has been shown to improve aerobic cycling performance in as little as 5 minutes, but with no effect when exercise began 60 or 120 minutes after consumption. A recent meta-analysis corroborates that the benefits of chewing gum are most evident in the first 15 minutes, even with a second peak in plasma caffeine concentration occurring 50 minutes after consumption.
Evidence in this area is limited, and further studies are needed to understand the timeline of caffeine’s effects across different modalities, the effectiveness of repeated dosing strategies, and how habitual consumption modulates these effects. Future research may consider extended-release caffeine products, which have shown slower absorption and more sustained plasma concentrations, prolonging benefits on mood and alertness, although their effects on physical performance remain to be investigated.
Innovative ways to administer caffeine for performance
Most of the current knowledge about the effects of caffeine on sport comes from studies where it is consumed in anhydrous form, in capsules or dissolved in liquids. However, more recent research is exploring the effectiveness of alternative methods such as chewing gum, nasal sprays, mouthwashes, and caffeinated gels and bars.
Some of these methods deserve investigation because they represent existing commercial products, while others may offer distinct logistical and mechanical advantages compared to traditional forms. Figure 2 illustrates the different modes of caffeine administration, indicating the level of evidence supporting its effects on physical performance.
The image presents a summary of the different modes of caffeine administration, with symbols indicating the current level of evidence supporting each statement, based on the authors’ expert opinion.
Although there is great individual variation and potential genetic influence, the maximum concentration of caffeine in blood plasma generally occurs about 60 minutes after ingestion. Therefore, most studies with capsules or liquids begin evaluating performance during this period. Caffeine chewing gum, in particular, has gained prominence due to its faster absorption and faster onset of pharmacological effects. It is suggested that caffeine is released from the gum and absorbed quickly through the oral mucosa.
Additionally, caffeinated mouthwash can generate a performance-enhancing effect by activating bitter taste receptors in the mouth, stimulating brain regions linked to information processing and reward. The ergogenic effect of caffeine is attributed to its action as an antagonist of adenosine receptors, which promotes an increase in excitatory neurotransmitters, and adenosine receptors are found in the oral cavity of mammals.
Consumption of caffeinated chewing gum demonstrated an initial peak in plasma concentration at approximately 10 minutes, followed by a second peak approximately 50 minutes later due to intestinal absorption. Growing evidence shows the positive effects of caffeinated gum on a variety of activities, such as endurance, anaerobic power, muscle strength, and cognitive function. A meta-analysis confirmed the potential of chewing gum, but highlighted that the benefits were more prevalent when exercise began within the first 15 minutes after consumption and were not as evident in untrained participants.
The ergogenic potential of caffeine mouthwash, where the substance is rinsed in the mouth for a few seconds without being swallowed, has also received attention. This method can mitigate problems with side effects from ingestion. Attributed to similar mechanisms to chewing gum, caffeine mouthwash has, in some cases, shown performance-enhancing effects in endurance activities, anaerobic exercise, muscle strength and cognitive function.
However, the evidence is less convincing compared to that for chewing gum. A recent systematic review indicated benefits in only 5 of the 15 studies evaluated, many with low methodological quality. Based on limited evidence, caffeinated mouthwash may be more effective when used repeatedly, rather than just once before exercise. Given the observed potential, more research is needed, focusing on frequency, duration and dose-response.
To date, only one study has evaluated the dose-response of mouthwash, showing that repeated rinses with a 3% caffeine solution (750 mg) increased repetitions to failure and reduced perceived exertion. Lower doses (1% or 2%) did not have the same effect. Future work should consider higher doses, possibly greater than those ingested, as the negative side effects of ingestion may not occur.
There is both favorable and conflicting evidence regarding the ergogenic potential of nasal sprays, dissolvable mouth strips, caffeine bars and gels. The limited number of studies, the lack of specific sporting context in many cases, and the variety of factors influencing the effects of caffeine preclude accurate conclusions about the efficacy and best practices for using these pathways. There is a substantial lack of evidence regarding nasal sprays, dissolvable mouth strips, and mouth aerosols, indicating the need for more research.
Despite the growing body of evidence for alternative modes of consumption, there is a lack of studies that directly compare the effectiveness between them. Some studies have indicated comparable effects of low doses of caffeine (80 mg) in coffee, energy drinks, capsules and dissolvable mouth strips on alertness, fatigue and reaction time. Others have shown similar effects of chewing gum, buccal strips and capsules (3–4.5 mg.kg⁻¹) on amateur running performance.
These studies, although informative, have important limitations, such as the lack of blinding in the treatment, which may have impacted the results due to expectations about caffeine. Furthermore, the period between ingestion and assessment was standardized at 15 minutes, which does not coincide with the peak plasma concentration for intestinal absorption methods. Therefore, future studies are needed to more precisely and directly compare the ergogenic effects of different modes of administration, considering a wider range of exercise intensities and modalities.
The influence of caffeine habituation and genotype on performance
Individual responses to caffeine are often variable, and factors such as genotype and habitual consumption can influence them. For a long time, it was believed that habitual caffeine intake impacted the ergogenic effect of supplementation. However, a recent meta-analysis pointed out that chronic caffeine consumption does not seem to affect the acute ergogenic effect, suggesting that doses of 3 to 6 mg·kg⁻¹ of body mass are beneficial for both individuals with high and low habitual consumption.
A summary of the impact of habituation was compiled from three different types of studies. When measuring consumption habits before procedures, there is evidence that supports or, in some cases, denies the ergogenic potential in habitual consumers. Compilation from these works is limited by several moderating factors that influence the response.
A more appropriate approach has been to use a between-subjects design to measure ergogenic response in participants stratified by drinking habits. Although these studies are limited, the general consensus is that caffeine is ergogenic regardless of habitual consumption. For example, research has shown that habitual intake level was not associated with the magnitude of improvement in 5K performance following coffee consumption.
Still, these results should be interpreted with caution. Different intake thresholds are used to stratify groups, which are often categorized by absolute caffeine intake rather than relative to body mass, due to challenges in accurate measurement. Furthermore, several factors may moderate the effect of caffeine, influencing comparisons between groups.
A within-subjects experimental design, where the ergogenic potential of caffeine is assessed before and after a period of prescribed intake, could be more appropriate. Studies using this approach are scarce and their results are controversial, with some evidence suggesting that chronic supplementation does not affect the acute response, while others show attenuating effects. The discrepancy is likely due to differences in prescribed dose, duration of intervention, and habitual caffeine use prior to the study.
Therefore, future research should continue to investigate the impact of caffeine habituation on its ergogenic potential, focusing on accurate measurements of drinking habits, dose specificity, and analysis of the impact of caffeine prescribed for longer periods. It is also essential to consider the genotype, given the association between polymorphisms in specific genes and the consumption habits and ergogenic effects of caffeine.
Two of the genes considered to have the greatest impact on the ergogenicity of caffeine are CYP1A2 and ADORA2A. Studies indicated that caffeine improved endurance performance in rapid caffeine metabolizers (CYP1A2 AA genotype) but had no effect or impaired performance in slow metabolizers (AC or CC genotypes). Other work supports this influence, but an equal number of studies have found no correlation.
Although polymorphisms in ADORA2A have been shown to influence caffeine sensitivity, studies evaluating their impact on physical performance are rare. Some research has shown that caffeine affected cycling performance in carriers of a specific allele (TT), but not in other groups. In contrast, the ADORA2A genotype did not influence strength performance in handball players. Clearly, further investigations are needed to explore the influence of the ADORA2A genotype and other genes, such as HTR2A, on sports performance.
There is evidence that the effects of genotype may be specific to exercise modalities and influenced by dose. However, work in this area is limited by the small sample size and the lack of scope in the modalities explored. Future studies should also look at optimizing intake periods based on CYP1A2 genotypes, as the current standardized approach may mask potential effects in slow metabolizers.
Caffeine as an ally in physical training adaptations
Considering the already established effects of acute caffeine intake on sports performance, it would be intuitive to think that improving or maximizing performance in an exercise session, multiplied throughout a well-planned training program, could generate more pronounced adaptations. Given the scarcity of direct evidence, this theory likely justifies the presence of high amounts of caffeine in pre-workout supplements.
To date, only five studies have analyzed the potential of chronic caffeine consumption to enhance adaptations to physical training, and only one of them focused on resistance exercise.
Using a double-blind, placebo-controlled, between-subjects study design, researchers demonstrated that supplementation with 201 mg (approximately 3 mg.kg⁻¹) of caffeine 60 minutes before each training session resulted in equivalent increases in maximal aerobic capacity (VO2peak) and time to exhaustion following an 8-week resistance training program. This was observed in non-specifically trained male and female participants.
On the other hand, other studies have shown that, in non-specifically trained participants, 3 mg.kg⁻¹ of caffeine consumed before each session caused superior improvements in maximal strength in squats and bench presses, compared to a placebo group, after a 6-week resistance training protocol. In contrast, other research, using the same dose and similar population, showed that changes in maximum strength after 4 weeks of training were similar between the placebo and caffeine groups, but the caffeine group showed more adaptations in lifting speed.
Yet another study demonstrated no benefit from caffeine supplementation used before resistance training during a 6-week intervention. However, comparisons were performed with only 5 participants in each of the caffeine and placebo groups, which limits the generalizability of the results.
In part, these previous studies are limited by small sample size, lack of quantification of an acute effect of caffeine, and, although a point of controversy, failure to consider the paradoxical impact of habituation to a repeated dose. Only one recent study, which examined the effect of pre-session ingestion of 3 mg.kg⁻¹ of caffeine in rugby players during a 7-week resistance training intervention, considered some of these factors.
Although caffeine had beneficial effects on muscle strength and an increase in total weight lifted throughout the intervention, the improvement in post-intervention muscle function was equivalent between the caffeine and placebo groups. The influence of habituation was ruled out as the acute effects of caffeine on measures of muscle function were still evident in the caffeine group. Although the training intervention used was effective, fixed load repetitions to failure protocols lack exercise progression and therefore are not the most effective approach to strength and power training, nor are they representative of athlete training regimens.
The small number of studies and ambiguous results regarding caffeine’s potential to enhance physical training highlight the need for more research in this area. It is critical to consider different exercise modalities, a variety of training methods, and a particular focus on measuring habituation to the prescribed dose. Such work should also consider the effect of caffeine as a training-enhancing supplement in a broader context, taking into account its impact on sleep, the importance of sleep for recovery, the specificity of caffeine’s timing of action, and the potential for a greater volume of work to exacerbate exercise-induced muscle damage.
The Effects of Caffeine on Muscle Damage and Post-Exercise Recovery
An important area of research that has received relatively little attention is the effect of caffeine on exercise-induced muscle damage (EIMD) and recovery. It has been suggested that caffeine intake could alleviate delayed onset muscle soreness (DOMS), mitigate temporary loss of muscle function, and decrease blood markers of muscle damage following injury-inducing exercise. However, as recently reviewed by a research group, the effects of caffeine intake on indirect markers of muscle damage are still limited and inconclusive.
Reasons for conflicting results include methodological differences, such as the methods for causing muscle damage, the muscle groups assessed, the experimental designs (between-subjects versus within-subjects), the caffeine supplementation protocol (single versus repeated intake; dosing), and the timing of ingestion in relation to the EIMD induction protocol. For example, it was hypothesized that caffeine ingested before a muscle injury-inducing protocol could attenuate that injury; however, when used after exercise-induced muscle injury (EIMD), it could alleviate symptoms, albeit acutely.
Alternatively, caffeine ingestion before exercise could result in an increase in total work performed, potentially increasing EIMD. Not all studies that aim to evaluate the effects of caffeine on EIMD have an experimental design that allows identifying whether caffeine exerts a protective effect against EIMD, merely alleviates symptoms during the recovery phase or even results in greater muscle damage due to its ergogenic effect. Therefore, caution is required when interpreting these studies and methodological aspects must be carefully considered.
Indirect markers of exercise-induced muscle injury (EIMD) include delayed onset muscle soreness (DOMS), blood markers (such as creatine kinase and lactate dehydrogenase), and muscle function (such as maximal voluntary isometric contraction). Some studies have shown that caffeine intake attenuated pain perception between 24 and 48 hours after the muscle injury protocol.
However, other investigations found contrasting results, with no difference between caffeine and placebo, or even higher DOMS in the caffeine group. The effects of caffeine intake on blood markers of EIMD are also controversial. Some studies have found lower circulating creatine kinase levels with caffeine, while others have found the opposite, i.e., higher levels. Most studies, however, found no significant differences between the placebo and caffeine groups in blood markers of EIMD.
Finally, four studies investigated the effects of caffeine on maximal voluntary contraction (MVC) after EIMD. One of them pointed out that caffeine intake resulted in a 10.2% higher MVC 48 hours after injury, compared to placebo. However, most studies have demonstrated no differences between caffeine and placebo conditions in MVC recovery after EIMD.
Taken together, research suggests that caffeine ingestion may result in reduced pain perception, but its effects on strength recovery after exercise-induced muscle training are still controversial. As mentioned, differences in EIMD protocol (e.g., matching of total work performed) and/or caffeine supplementation regimen (such as timing of intake, single or repeated doses) may explain discrepancies between studies. It is not yet clear whether ingesting caffeine before exercise has a protective effect.
However, due to its acute effects on muscular performance and pain perception, caffeine consumption may be a valid strategy for recovery between intense exercise sessions. Future studies should further investigate the effects of caffeine intake at different times in relation to AMD (before or after) and different supplementation protocols (dose, single or continuous supplementation, form of administration, etc.). Figure 3 illustrates different supplementation regimens that should be considered when interpreting studies on the effect of caffeine on EIMD.
The image illustrates different supplementation regimens that should be considered when interpreting studies on the effect of caffeine on exercise-induced muscle damage.
Furthermore, a challenging but promising area of study involves understanding the mechanisms of action that may be involved in the effect of caffeine on EIMD. Thus, it will be possible to understand whether caffeine can exert a protective effect (for example, at a cellular level) against muscle damage, or simply act as an ergogenic aid, improving contractile function after exercise-induced muscle damage.
